This research program is centered around the application of protein crystallography (a form of microscopy which uses X-rays in place of light rays) to directly produce high resolution images of protein structure. Most of our research effort has been aimed at achieving a more detailed understanding of the relationships between hemoglobin structure and function. In particular, we have determined the structures of a number of mutant and chemically modified hemoglobins. By identifying the differences between the structures of these abnormal hemoglobins and normal human deoxyhemoglobin we have been able to 1) pinpoint structural features which are essential for the full expression of hemoglobin function, 2) suggest a structural basis for the action of a number of drugs which have been shown to be effective in reducing the polymerization of sickle cell hemoglobin, and 3) uncover anion binding sites which may be important in the interaction of hemoglobin with CO2. We have also succeeded in growing crystals of aspartate aminotransferase that are suitable for high resolution X-ray analysis. The structure of this enzyme is of general interest since it is representative of a large class of enzymes which use pyridoxal phosphate as a coenzyme and operate by a "ping-pong" mechanism. BIBLIOGRAPHIC REFERENCES: Arnone, A., Gacon, G., and Wajcman, H., "X-ray and Functional Studies of Hemoglobins Nancy and Cochin-Port Royal", (1976), J. Biol. Chem., 251, 5875-5880. Arnone, A. and Williams, D., "X-ray Diffraction Studies of Sulfate Binding Sites in Crystalline Deoxyhemoglobin using Selenate Exchange", (1977) Fed. Proc. 36, 2554.